CODSWALLOP

Carbonic anhydrase 2

Homo sapiens · seed P00918 · 260 aa · family defined as ≥30% identity to that seed · compiled 09 August 2026

1,490Entries
1,490Polymer entities
232Distinct constructs
18Organisms
1,403Ligand-bound
0.90 ÅBest resolution
1.52 ÅMedian resolution

Every figure here is counted over the whole family rather than quoted from one entry.

Constructs, most-used first

232 distinct constructs across 1,490 entries. 771 polymer entities differ from the UniProt canonical sequence in some way, 40 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
566 260 0.90 3K34 matches the canonical sequence
119 259 0.95 1LUG residues 2-260
58 257 1.10 5NXW residues 4-260
54 265 0.93 6ROB matches the canonical sequence
45 260 0.95 6YZN A65S, N67Q, E69T +4 more
44 257 1.12 6OTK residues 4-260; A65S, N67Q, E69T +4 more
39 258 1.00 4Q78 residues 3-260
32 261 1.24 7Q0D matches the canonical sequence
29 263 1.12 9F2O residues 29-291; G29M
22 262 1.05 30TA matches the canonical sequence
15 263 1.06 5OGJ matches the canonical sequence
14 260 1.55 2FOY residues 2-261
12 257 1.75 6G9U residues 135-391; D136P, C174S
12 259 1.80 1I9Q residues 2-260; F130V
12 260 1.04 7U5X S2A
11 260 1.07 4Q08 A65S, N67K, I91T +3 more
11 274 1.10 8Q3U His6; C185S, C219S
9 260 1.45 3OKV A65S, N67Q
9 263 1.19 9R0U residues 29-291; G29A
9 266 1.72 3FW3 residues 19-284
8 260 1.05 1MOO H64A
8 260 1.54 2CBA matches the canonical sequence
7 257 1.98 7POM residues 135-391; D136P, C174S, N346Q
7 260 1.14 8RNS A65S, N67K, E69N +6 more
6 243 2.15 8DYQ His6; 1 internal deletion; M1V, S23G, A24S +2 more

Showing the 25 most-used of 232.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

A65S 27% N67Q 25% I91L 25% L203A 23% E69T 23% F130V 22% C205S 18% V134A 17% K153N 16% G182T 16% K111G 16% V222L 16% R181S 16% A247T 16% H36S 16% T37E 15% Q103H 15% Q254T 15% K256R 15% Q53P 15% L100T 15% G155A 15% N252G 15% K24N 15% E26N 15% G102D 15% W244F 15% V160L 15% D34K 14% Q74D 14%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 1,376 92.3%
dimeric2 92 6.2%
tetrameric4 11 0.7%
trimeric3 8 0.5%
hexameric6 2 0.1%
pentameric5 1 0.1%

911 entries have the depositor's assembly corroborated by PISA, 538 carry the depositor's word alone and 41 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 5 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1Y7W, 3L14, 4LP6, 4Q0L, 5KU6.

Domain architecture

DomainSourceSpan (seed)Chains
Alpha carbonic anhydraseCATH 3.10.200.10 4–260 864
Carbonic anhydraseSCOP2B 8036258 4–260 1,149
Carbonic anhydraseSCOP2B 8034342 7–260 39
Carbonic anhydraseSCOP2B 8042916 9–260 42
Carbonic anhydraseSCOP2B 8065103 10–260 31
Carbonic anhydraseSCOP2B 8065111 10–260 18

What binds it

ComponentClassNameEntriesBest (Å)
ZNcofactor Zinc Ion 1,394 0.90
GOLcryoprotectant Glycerol 427 0.90
DMScryoprotectant Dimethyl Sulfoxide 237 0.94
HGion Mercury (Ii) Ion 154 0.93
EDOcryoprotectant 1,2-Ethanediol 84 0.99
MBOligand Mercuribenzoic Acid 82 0.95
SO4ion Sulfate Ion 79 1.20
NAion Sodium Ion 59 0.94
CO2solvent Carbon Dioxide 52 0.90
BE7ligand (4-Carboxyphenyl)(Chloro)mercury 51 0.93
BCNbuffer Bicine 45 0.98
BCTbuffer Bicarbonate Ion 42 0.90
CLion Chloride Ion 39 1.03
ACTcryoprotectant Acetate Ion 33 1.01
AZMligand 5-Acetamido-1,3,4-Thiadiazole-2-Sulfonamide 31 1.10
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 30 1.06
TRSbuffer 2-Amino-2-Hydroxymethyl-Propane-1,3-Diol 28 1.09
PEGcryoprotectant Di(Hydroxyethyl)ether 28 0.99
BGCligand Beta-D-Glucopyranose 27 0.93
NIion Nickel (Ii) Ion 26 1.20

How it crystallises

Parsed from the free text 1,369 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,388 entries that recorded anything at all. Median pH 7.8 (range 4.0 to 11.0).

Precipitants

Sodium citrate × Ammonium sulfate × PEG × Sodium malonate × Sodium chloride × Magnesium chloride × Lithium sulfate × Calcium chloride × PEG (unspecified) × Isopropanol ×

Buffers

Tris × Citrate × Sodium acetate × HEPES × MES × Glycine × Imidazole × Bis-Tris × CAPS × Bis-Tris propane × Phosphate × Sodium cacodylate ×

Which entries to trust

1,490 entries carry a wwPDB validation report: 1,170 clean, 277 worth a check and 43 with something to explain. Median clashscore 3.9, median RSRZ outliers 1.94%, median R-free minus R-work 0.031. 1,359 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,423 0.90 1341 100%
Bos taurus14 1.23 14 100%
Schistosoma mansoni10 1.60 10 92%
Mus musculus9 1.88 9 99%
Neisseria gonorrhoeae8 1.90 8 97%
Orthopoxvirus vaccinia5 1.42 0 85%
Unknown5 1.75 5 100%
Persephonella marina EX-H13 2.00 3 96%
Thermovibrio ammonificans2 1.69 2 97%
Chlamydomonas reinhardtii2 2.60 2 96%
Photobacterium profundum SS91 1.50 1 96%
Thermovibrio ammonificans HB-11 1.55 1 97%

Seed sequence

260 residues. Every identity figure in this document is measured against this sequence.

MSHHWGYGKHNGPEHWHKDFPIAKGERQSPVDIDTHTAKYDPSLKPLSVSYDQATSLRILNNGHAFNVEFDDSQDKAVLKGGPLDGTYRLIQFHFHWGSLDGQGSEHTVDKKKYAAELHLVHWNTKYGDFGKAVQQPDGLAVLGIFLKVGSAKPGLQKVVDVLDSIKTKGKSADFTNFDPRGLLPESLDYWTYPGSLTTPPLLECVTWIVLKEPISVSSEQVLKFRKLNFNGEGEPEELMVDNWRPAQPLKNRQIKASFK

Primary citations

One record per paper, not per entry.

YearCitation
2026 1-Aryl-6,7-Dimethoxy-3,4-Dihydroisoquinoline-2(1H)-Sulfonamides as hCA XII Selective Inhibitors: Experimental and Theoretical Studies to Interrogate the Isoform Selectivity. Chemmedchem doi:10.1002/cmdc.70390
2026 X-ray analysis of complexes of carbonic anhydrase II with 1,3-oxazole-containing sulfonamide derivatives elucidates the structural basis for their exceptionally high inhibitory potency. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X26002128
2026 Discovery of a Mixed and Prodrug-Like Inhibition Mechanism for Phosphocoumarins and Phosphoquinolinones against Human Carbonic Anhydrases. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00915
2026 Achieving femtomolar affinities in structure-based drug design. Eur.Biophys.J. doi:10.1007/s00249-025-01812-5
2025 X-ray crystallographic and kinetic studies of biguanide containing aryl sulfonamides as carbonic anhydrase inhibitors. Rsc Med Chem doi:10.1039/d4md01018c
2025 Design of Rigid Compounds to Enhance Selectivity for Carbonic Anhydrase IX. Chemistry doi:10.1002/chem.202404409
2025 Di- meta -Substituted Fluorinated Benzenesulfonamides as Potent and Selective Anticancer Inhibitors of Carbonic Anhydrase IX and XII. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01142
2025 Affinity and Selectivity of Protein-Ligand Recognition: A Minor Chemical Modification Changes Carbonic Anhydrase Binding Profile. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01421
2025 Fast product release requires active-site water dynamics in carbonic anhydrase. Nat Commun doi:10.1038/s41467-025-59645-x
2025 Depsides from Origanum dictamnus and Satureja pilosa as selective inhibitors of carbonic anhydrases: Isolation, structure elucidation, X-ray crystallography. Arch Pharm doi:10.1002/ardp.202400823
2025 An ureido-substituted benzenesulfonamide carbonic anhydrase inhibitor exerts a potent antitumor effect in vitro and in vivo. Exp Hematol Oncol doi:10.1186/s40164-025-00690-z
2025 Conformational flexibility of His200 enables catalytic activity in the T200H mutant of carbonic anhydrase II. Mol.Cells doi:10.1016/j.mocell.2025.100226
2025 Dual inhibition of carbonic anhydrase IX and glutathione peroxidase 4 as a novel strategy for ferroptosis-induced tumor cell death. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.118107
2025 Structural Studies of the Dopamine D 4 Receptor Antagonist Sonepiprazole as an Inhibitor of Human Carbonic Anhydrases. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00034
2025 Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond. Arch Pharm doi:10.1002/ardp.202400776
2025 Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00562
2025 Off-target binding of the histone deacetylase inhibitor vorinostat to carbonic anhydrase II and IX. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X25007447
2025 Targeting Human Carbonic Anhydrases with Novel Piperazine and Homopiperazine Benzenesulfonamides to Alleviate Paclitaxel-Induced Peripheral Neuropathy. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02626
2025 O-derivatization of natural tropolone and beta-thujaplicin leading to effective inhibitors of human carbonic anhydrases IX and XII. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.117552
2025 Protein crystallization and structure determination at room temperature in the CrystalChip. Febs Open Bio doi:10.1002/2211-5463.13932
2025 Design, anticancer activity, and mechanistic evaluation of a novel class of selective human carbonic anhydrase IX inhibitors featuring a trifluorodihydroxypropanone pharmacophore. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.118043
2025 Structure-based design of an aromatic helical foldamer-protein interface. Chem Sci doi:10.1039/d5sc01826a
2024 Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00341
2024 Exploring the binding mode of phenyl and vinyl boronic acids to human carbonic anhydrases. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2024.136873
2024 Novel Carbonic Anhydrase Inhibitors with Dual-Tail Core Sulfonamide Show Potent and Lasting Effects for Glaucoma Therapy. J.Med.Chem. doi:10.1021/acs.jmedchem.3c02254
2024 From X-ray crystallographic structure to intrinsic thermodynamics of protein-ligand binding using carbonic anhydrase isozymes as a model system. Iucrj doi:10.1107/S2052252524004627
2024 Inhibition of Pseudomonas aeruginosa Carbonic Anhydrases, Exploring Ciprofloxacin Functionalization Toward New Antibacterial Agents: An In-Depth Multidisciplinary Study. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01555
2024 Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00284
2024 Sulfonamide-incorporated bis( alpha-aminophosphonates) as promising carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and X-ray crystallographic studies. Arch Pharm doi:10.1002/ardp.202400038
2024 XFEL structure of carbonic anhydrase II: a comparative study of XFEL, NMR, X-ray and neutron structures. Acta Crystallogr D Struct Biol doi:10.1107/S2059798324000482
2024 Controlling the incorporation of fluorinated amino acids in human cells and its structural impact. Protein Sci. doi:10.1002/pro.4910
2024 Benzoxaborinine, New Chemotype for Carbonic Anhydrase Inhibition: Ex Novo Synthesis, Crystallography, In Silico Studies, and Anti-Melanoma Cell Line Activity. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01516
2024 The dopamine D 2 receptors antagonist Veralipride inhibits carbonic anhydrases: solution and crystallographic insights on human isoforms. Chem Asian J doi:10.1002/asia.202400067
2024 Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX. Elife doi:10.7554/eLife.101401
2024 Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00443
2024 Machine Learning-Enhanced Quantum Chemistry-Assisted Refinement of the Active Site Structure of Metalloproteins. Inorg.Chem. doi:10.1021/acs.inorgchem.4c01274
2024 4-(Pyrazolyl)benzenesulfonamide Ureas as Carbonic Anhydrases Inhibitors and Hypoxia-Mediated Chemo-Sensitizing Agents in Colorectal Cancer Cells. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01894
2024 Microsecond Timescale Conformational Dynamics of a Small-Molecule Ligand within the Active Site of a Protein. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202313947
2024 Thia- and Seleno-Michael Reactions for the Synthesis of Carbonic Anhydrases Inhibitors. Chemmedchem doi:10.1002/cmdc.202400345
2024 Directed Evolution of an Artificial Hydroxylase Based on a Thermostable Human Carbonic Anhydrase Protein Acs Catalysis doi:10.1021/acscatal.4c04163